Correlation of peripapillary retinal nerve fiber layer and macular ganglion cell-inner plexiform layer in early to moderate glaucoma using the Cirrus ® widefield analysis (PanoMap ® ).

PURPOSE: To evaluate and correlate the structural changes between peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell layer (GCL) + inner plexiform layer (IPL) in different stages of glaucoma using PanoMap ® optical coherence tomography (OCT). DESIGN: Retrospective observational study. METHODS: Glaucoma diagnostic test data were collected from early to moderate open-angle glaucoma patients. The average and minimum GCL + IPL thickness, sectoral GCL + IPL thickness, and the average and sectoral RNFL thickness were correlated with the different glaucoma stages. RESULTS: This study included 157 eyes from 157 glaucoma patients. Patients were grouped into pre-perimetric, early, and moderate glaucoma. The mean average RNFL thickness, RNFL thickness per sector, average GCL + IPL thickness, and minimum GCL + IPL thickness were different between the three groups ( P < 0.001), except for the nasal sector ( P = 0.643). The mean GCL + IPL thickness in all six sectors showed differences between the groups ( P < 0.001), except the superonasal sector ( P < 0.002). The inferior GCL + IPL sector is the thinnest, followed by the inferotemporal sector. There was a strong correlation between the mean average RNFL and the average GCL + IPL thickness in the pre-perimetric group ( r = 0.4963, P < 0.001) and the moderate group ( r = 0.6534, P < 0.001). The early glaucoma group did not show significant correlation ( r = 0.2963, P = 0.0536). CONCLUSION: Peripapillary RNFL and macular GCL + IPL thinning was evident in different stages of glaucoma, with more thinning observed with increasing glaucoma severity. The peripapillary RNFL and macular GCL + IPL average thickness values were highly correlated in the pre-perimetric and moderate stages of glaucoma.

Outcomes of primary trabeculectomy with mitomycin-C for primary angle closure glaucoma among supervised trainees in a tertiary eye center in Manila.

PURPOSE: To evaluate efficacy and safety of trabeculectomy with mitomycin C (trab-MMC) for primary angle closure glaucoma (PACG) performed by ophthalmology trainees. METHODS: This was a six-year retrospective study of patients with primary trab-MMC with PACG performed by ophthalmology trainees in a tertiary urban eye center. Outcomes included intraocular pressure (IOP), number of medications, and complications. RESULTS: There were 120 PACG eyes that underwent trab-MMC performed by trainees. The mean follow-up duration was 28.6 ± 20.8 months. At 24 months, postoperative IOP decreased from 32.1 ± 12.0 mm Hg to 14.8 ± 6.9 mm Hg (p<0.0001) with decrease in glaucoma medications [0 (0), 0-2; p<0.0001]. Half of surgeries, 64/120 (53.8%) utilized MMC-onlay and the other half, 55/120(46.2%) received MMC sub-tenon injection. Half 60/120 (50.4%) utilized releasable sutures. Majority 55/120 (46.2%) utilized conjunctival closure near the corneal limbus while 34/120 (28.6%) used a conjunctival skirt. Cumulative complete surgical success rates were 63.3%, 55.83%, and 42.5% at 6, 12, and 24 months, respectively. Most complications were minor, including high IOP (25.0%), bleb leaks (13.3%), and cystic blebs (15.0%). Bleb needling was the most common (24.2%) post-op surgical intervention. CONCLUSION: Among supervised ophthalmology trainees in the Philippines, trab-MMC for PACG was effective in lowering IOP long term and decreasing glaucoma medications, and surgical success rates were generally comparable with trainee studies from first world nations. Complications were minor and not sight threatening.

Towards label-free 3D segmentation of optical coherence tomography images of the optic nerve head using deep learning.

Recently proposed deep learning (DL) algorithms for the segmentation of optical coherence tomography (OCT) images to quantify the morphological changes to the optic nerve head (ONH) tissues during glaucoma have limited clinical adoption due to their device specific nature and the difficulty in preparing manual segmentations (training data). We propose a DL-based 3D segmentation framework that is easily translatable across OCT devices in a label-free manner (i.e. without the need to manually re-segment data for each device). Specifically, we developed 2 sets of DL networks: the 'enhancer' (enhance OCT image quality and harmonize image characteristics from 3 devices) and the 'ONH-Net' (3D segmentation of 6 ONH tissues). We found that only when the 'enhancer' was used to preprocess the OCT images, the 'ONH-Net' trained on any of the 3 devices successfully segmented ONH tissues from the other two unseen devices with high performance (Dice coefficients > 0.92). We demonstrate that is possible to automatically segment OCT images from new devices without ever needing manual segmentation data from them.

Investigating the neuroprotective effect of Copolymer-1 in acute primary angle closure - Interim report of a randomized placebo-controlled double-masked clinical trial.

PURPOSE: To investigate the neuroprotective effect of Copolymer-1 (Cop-1) in patients with acute primary angle closure (APAC) in a randomized double-masked controlled trial. METHODS: After initial medical management, APAC patients were randomized to receive either subcutaneous Cop-1 or placebo within 24 hr and at 1 week. After laser peripheral iridotomy (LPI), subjects underwent serial visual field (VF) tests and retinal nerve fibre layer (RNFL) thickness measurements with spectral-domain optical coherence tomography. The primary outcome measure was mean number of progressing points (significant slope of ≥ 1 dB per year sensitivity loss) over 16 weeks based on pointwise linear regression analysis, and the secondary outcome measure was the change in RNFL thickness. RESULTS: Thirty-eight patients (19 in each group) completed the study. Twenty-five (65.8%) were female, the majority being Chinese (86.8%) with mean age 62.5 years (SD 8.1). Patients in the Cop-1 group were found to have mean of 0.32 (SD 0.95) progressing points compared to 2.74 (SD 5.31) in the placebo group (p = 0.09), while 3/19 (15.8%) of Cop-1 treated patients had 1 or more progressing points compared to 7/19 (36.8%) in the placebo group (p = 0.14). There was no difference in change of RNFL thickness between groups (p = 0.57). We found improvement of mean deviation (MD) at week 16 in the Cop-1 group (p = 0.01) compared to worsening of MD in the placebo group (p = 0.04). CONCLUSION: After APAC, there was no difference in VF progression (or RNFL thickness change) between Cop-1 and placebo groups. However, there was improvement of MD in Cop-1 treated patients.

Enhancement of Visual Field Predictions with Pointwise Exponential Regression (PER) and Pointwise Linear Regression (PLR).

PURPOSE: The study was conducted to evaluate threshold smoothing algorithms to enhance prediction of the rates of visual field (VF) worsening in glaucoma. METHODS: We studied 798 patients with primary open-angle glaucoma and 6 or more years of follow-up who underwent 8 or more VF examinations. Thresholds at each VF location for the first 4 years or first half of the follow-up time (whichever was greater) were smoothed with clusters defined by the nearest neighbor (NN), Garway-Heath, Glaucoma Hemifield Test (GHT), and weighting by the correlation of rates at all other VF locations. Thresholds were regressed with a pointwise exponential regression (PER) model and a pointwise linear regression (PLR) model. Smaller root mean square error (RMSE) values of the differences between the observed and the predicted thresholds at last two follow-ups indicated better model predictions. RESULTS: The mean (SD) follow-up times for the smoothing and prediction phase were 5.3 (1.5) and 10.5 (3.9) years. The mean RMSE values for the PER and PLR models were unsmoothed data, 6.09 and 6.55; NN, 3.40 and 3.42; Garway-Heath, 3.47 and 3.48; GHT, 3.57 and 3.74; and correlation of rates, 3.59 and 3.64. CONCLUSIONS: Smoothed VF data predicted better than unsmoothed data. Nearest neighbor provided the best predictions; PER also predicted consistently more accurately than PLR. Smoothing algorithms should be used when forecasting VF results with PER or PLR. TRANSLATIONAL RELEVANCE: The application of smoothing algorithms on VF data can improve forecasting in VF points to assist in treatment decisions.

Determinants of pupil diameters and pupil dynamics in an adult Chinese population.

BACKGROUND: To investigate the determinants of pupil diameter (PD), amplitude of pupil diameter change (PD-change) and speed of pupil constriction (SPC) using video anterior segment optical coherence tomography (AS-OCT) in a population-based sample of Chinese adults. METHODS: Chinese adults aged 40 to 80 years who were free from glaucoma were consecutively recruited from the population-based Singapore Chinese Eye Study. The SPC was measured by AS-OCT videography. Univariate and multivariate analyses were performed to examine the effects of demographic and ocular biometric factors (e.g., axial length [AL], anterior chamber depth [ACD], baseline PD, iris thickness at the area of the dilator muscle [ITDMR], iris area [IA], and iris bowing [IB]) on SPC, PD, and PD-change. RESULTS: A total of 266/302 (89.5 %) AS-OCT videos of eligible eyes were available for analysis. Among these subjects, 64.3 % were women, and the mean age (± standard deviation [SD]) was 56 ± 8.3 years. SPC was not associated with sex. In multiple regression analyses, SPC was independently associated with baseline PD (ß = 0.116, p = 0.006). Baseline PD was independently associated with ACD (ß = 0.341, p < 0.001), TISA 500 (ß = -4.513, p < 0.001), IA (ß = -2.796, p < 0.001), and ITDMR (ß = 6.573, p < 0.001). PD-change was independently associated with ACD (ß = 0.256, p < 0.001), IA (ß = -1.507, p < 0.001), IB (ß = 0.630, p = 0.011), and ITDMR (ß = 3.124, p < 0.001). CONCLUSIONS: Among normal eyes in an adult Chinese population, SPC was associated with larger baseline PD. Larger baseline PD and greater PD change form dark to light were associated with greater ACD, with smaller IA and thicker ITDMR.

Determinants of optical coherence tomography-derived minimum neuroretinal rim width in a normal Chinese population.

PURPOSE: To characterize an optical coherence tomography (OCT)-derived parameter, Bruch's membrane opening-minimum rim width (BMO-MRW), and its association with demographic and clinical parameters in normal Chinese subjects. METHODS: Right eyes of 466 consecutive healthy subjects from a population-based study of Singaporean Chinese underwent Cirrus OCT imaging. The retinal internal limiting membrane (ILM) and BMO were automatically delineated using the built-in Cirrus algorithm. The standard 36 interpolated radial B-scans (72 BMO points, 5° increments) of each optic nerve head were manually extracted from the central circle (3.46-mm diameter). We used Matlab to measure the shortest distance from the BMO points to the ILM. Associations of BMO-MRW with demographic and clinical parameters were evaluated using marginal general estimating equations analysis. RESULTS: There was a slight preponderance of male subjects (50.9%), with a mean age of 54.8 ± 7.63 years. Mean BMO-MRW was 304.67 ± 58.96 µm (range, 173.32-529.23 µm), which was highly associated with OCT-derived disc area (DA) (ß = -91.78, P < 0.001) and rim area (RA) (ß = 194.31, P < 0.001), followed by spherical refractive error (SRE) (ß = -2.23, P = 0.02) and retinal nerve fiber layer (RNFL) thickness (ß = 0.5, P = 0.04), after adjusting for the associated factors such as age, sex, intraocular pressure (IOP), and vertical cup-disc ratio (VCDR). CONCLUSIONS: Disc area and RA had the strongest association with BMO-MRW, followed by SRE and RNFL thickness. The availability of this normative database will facilitate optic nerve head assessment using the BMO-MRW parameter in Chinese subjects.

Retinal vascular caliber between eyes with asymmetric glaucoma.

PURPOSE: To compare differences in retinal arterial and venular caliber (RAC and RVC respectively) between fellow eyes with glaucoma of asymmetric severity. METHODS: We included subjects with bilateral primary glaucoma that had vertical cup-disc ratios (VCDR) >0.2 between both eyes, or visual field (VF) mean deviation (MD) >6.0 decibels (dB) between both eyes. RESULTS: Among 158 subjects, the average RAC in glaucoma eyes was 131.5 ± 17.8 µm vs 141.6 ± 18.8 µm in fellow eyes with mild disease (p < 0.001). RVCs in glaucoma eyes were 201.0 ± 21.4 µm vs 211.7 ± 25.3 µm in fellow eyes with mild disease (p < 0.001). This relationship held in clustered linear regression models adjusted for age, gender, vascular risk factors, visual acuity, axial length, and intraocular pressure, with RVCs narrower in eyes with worse disease vs mild disease. Eyes with worse disease had greater VCDR (0.9 ± 0.1 vs 0.7 ± 0.1, p < 0.001), and worse VF MD (-18.5 ± 8.6 vs -6.6 ± 5.6, p < 0.001). CONCLUSION: In glaucoma with asymmetric severity between fellow eyes, retinal vascular caliber is less in the eye with more severe disease.

Understanding structure and function in glaucoma

OBJECTIVE: Glaucomatous optic neuropathy (GON), defined as definitive damage to the optic-nerve head (ONH) and retinal-nerve-fiber layer (RNFL), involves structural changes in the ONH and RNFL and functional losses in the central visual field. Due to the unique anatomic distribution of the nerve fibers as they enter the ONH, there are specific changes in the ONH correlated with specific findings in the visual-field characteristic of GON. The evaluation of these changes is discussed. METHODS: There are qualitative and quantitative methods in the structural examination of the ONH and RNFL, and quantitative techniques in the functional assessment of the central visual field. They are correlated to one another their strengths and limitations are discussed. RESULTS: Clinical evaluation of the ONH and RNFL consists of five basic rules: (1) identify the limits of the optic disc and determine its size, (2) identify the s of the neuroretinal rim, (3) examine the RNFL, (4) examine the region for parapapillary atrophy, and (5) look for retinal and optic-disc hemorrhages. These steps are simple to use and comprise a portion of the comprehensive eye evaluation. Without proper documentation of the changes in glaucoma progression may be missed. Computer-based digital-imaging technology exemplified by the HRT II, GDx, OCT, provides fast, reproducible, objective measurements of the ONH and RNFL, allowing for more precise diagnosis and monitoring of glaucoma. These changes have good correlation to functional assessments exemplified by the standard automated perimetry (SAP) and the selective perimetry (FDT, SWAP). Typical glaucomatous visu field defects include nasal step, paracentral scotoma, and arcuate defects which follow the RNFL pattern. Progression of these defects is monitored over time and needs to be differentiated from long-term fluctuation. CONCLUSION: The clinician should perform both structural and functional assessments to diagnose and monitor glaucoma. Both examinations provide complimentary information and each has its own place in the clinical care of glaucoma patients. The newer imaging devices and selective perimetry augment the diagnostic armamentarium of the clinician and should, therefore, be used appropriately.

What is the optimal surgical management?

OBJECTIVE: Since cataract and glaucoma often coexist, and there is no agreement as to their optimal management, a review of the surgical strategies for coexisting I cataract and glaucoma is necessary. The latest evidence-based findings from various studies are presented. METHODS: A literature search of the latest full articles (up to September 2006) was conducted on the surgical management of coexisting cataract and glaucoma. The results of the 2001 Johns Hopkins milestone study were also included for analysis and comparison. RESULTS: Evidence is strong that trabeculectomy is associated with increased risk of postoperative cataract. Though cataract surgery alone may be appropriate for some glaucoma patients, combined cataract and glaucoma surgery lower long-term intraocular pressure (IOP) more than cataract extraction alone. Use of intraoperative mitomycin-C is beneficial in combined surgery. Limbu and fornix-based conjunctival flaps are equally effective for lowering IOP combined surgery. Trabeculectomy alone lowers long-term IOP more tha combined extracapsular cataract extraction (ECCE) and trabeculectomy. Evidence is weak that combined surgery with phacoemulsification rather than ECCE results in lower long-term IOP, as does two-site compared to single-site combined surgery. CONCLUSION: The literature does not point to an optimal strategy for controlling in patients with coexisting cataract and glaucoma needing surgery. There is a continued need for high-quality studies of longer duration and more information on the optic nerve and visual field.

Glaucoma in retinoblastoma.

The association between retinoblastoma and secondary glaucoma is well known. The most common cause of secondary glaucoma in retinoblastoma is iris neovascularization (NVI) followed by pupillary block and tumor seeding of the anterior chamber. Although glaucoma is a secondary clinical issue in retinoblastoma (RB) management and care, awareness of its presence, revealed by a thorough ocular exam of the anterior segment, can guide the clinician in assessing the overall condition of the affected eye.

Selective laser trabeculoplasty.

Selective laser trabeculoplasty (SLT) has been shown to be safe, well tolerated, and effective in intraocular pressure (IOP) reduction as therapy in several forms of open-angle glaucoma. The preservation of trabecular meshwork (TM) architecture and the demonstrated efficacy in lowering IOP make SLT a reasonable and safe alternative to argon laser trabeculoplasty (ALT). SLT may also be effective for cases of failed ALT and is a procedure that may also be repeatable, unlike ALT. SLT is also a simple technique for an ophthalmologist to learn as the large spot size eliminates the need to locate a particular zone of treatment on the TM. SLT has been demonstrated to be effective as primary treatment for open angle glaucoma and can be an effective adjunct in the early treatment of glaucoma. Furthermore, SLT can be considered as a primary treatment option in patients who cannot tolerate or who are noncompliant with their glaucoma medications, without interfering with the success of future surgery.

YAG laser rate for posterior capsular opacification (PCO) using varied IOL materials

This study aims to determine the average span of time for Nd:YAG Capsulotomy for posterior capsular opacification after phacoemulsification using four (4) different posterior chamber intraocular lens (IOL) materials (acrylic, polymethylmethacrylate, silicone and hydrogel). This is a retrospective, cohort study wherein data from the charts of 46 patients of a single surgeon were tabulated. All the patients underwent a standardized and an uncomplicated phacoemulsification for senile cataracts with posterior chamber IOL insertion. There were a total of 50 IOLs in this study, 8 acrylic, 16 polymethylmethacrylate (PMMA), 24 silicone and 2 hydrogel. The average duration before Nd: YAG capsulotomy was necessary for each IOL material were: acrylic 11.91 months, PMMA 14.50 months, silicone 18.25 months and hydrogel 8.125 months. This study revealed that each of the four (4) different IOL materials had no influence on the span of time before the necessity for Nd: YAG capsulotomy. (Author)

Cup to disc ratio and optic disc size in screening for glaucoma

PURPOSE:To determine the cup and disc areas using computer-aided imaging. METHODOLOGY:Case-control study using the computer-aided imaging as a screening test in a given population. RESULTS:There is a wide variability in cup and disc areas among glaucoma suspects and normal. CONCLUSION:C:D alone has a poor predictive value for diagnosing glaucoma.Optic disc size with C:D is just as sensitive and specific in screening for glaucoma.Cup and disc areas are positively correlated for normal and glaucoma suspects.